1-O-acetyl-5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-4-thio-L-ribofuranose | 189998-53-6

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: 1-O-acetyl-5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-4-thio-L-ribofuranose
• 英文别名: [(5R)-5-[[tert-butyl(diphenyl)silyl]oxymethyl]thiolan-2-yl] acetate
• CAS: 189998-53-6
• 化学式: C₂₃H₃₀O₃SSi
• 分子量: 414.641
• InChiKey: XTOYTTNREVGAJY-LCQOSCCDSA-N

物化性质

• 沸点：
  469.6±45.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.35
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  60.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-O-acetyl-5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-4-thio-L-ribofuranose 在 叠氮化锂 、 二氯乙基铝 、 sodium hydride 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 2,6-Diazido-9-[(2R,5R)-5-(tert-butyl-diphenyl-silanyloxymethyl)-tetrahydro-thiophen-2-yl]-9H-purine
  参考文献：
  名称：

  Synthesis of a Series of Purine 2′,3′-Dideoxy-L-Nucleoside Analogues as Potential Antiviral Agents

  摘要：

  Various 2',3'-dideoxy-L-nucleoside analogues, 6-amino-9-(2,3-dideoxy-beta-L-ribofuranosy))purine (19), 2-chloro-6-amino-9-(2,3-dideoxy-beta-L-ribofuranosyl)-purine (20), 2-chloro-6-amino-9-(2,3-dideoxy-4-thio-beta-L-ribofuranosyl)purine (21), 2,5- diamino 9-(2,3-dideoxy-beta-L-ribofuranosyl)purine (26), 2,6-diamino-9-(2,3-dideoxy-4-thio-beta-L-ribofuranosyl)-purine (27), 2-amino-6-chloro-9-(2,3-dideoxy-beta-L-ribofuranosyl)purine (28), (6-chloro-9-(2,3-dideoxy-4-thio-beta-L-ribofuranosyl)purine (29), and 6-amino-9-(2,3-dideoxy-4-thio-beta-L-ribofuranosyl)purine (30) have been synthesized by coupling of the sodium salt of 2-amino-6-chloropurine (1), 6-chloropurine (2), and 2,6-dichloropurine urine (3) with 1-O-acetyl-5-O-(tert-butyldimethylsilyl)-2,3-dideoxy-L-ribofuranose (4) or 1-O-acetyl-5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-4-thio-L-ribofuranose (5) in anhydrous MeCN in the presence of either EtAlCl(2) or Et(2)AlCl followed by separation of the alp-anomers and deprotection of the blocking groups. However, the synthesis of 9-(2,3-dideoxy-beta-L-ribofuranosyl)guanine (57, beta-L-ddG) was not straightforward. Coupling of the silylated N-2-palmitoylguanine (48) with sugar 4 in anhydrous MeCN, using trimethylsilyl trifluoromethanesulfonate as a catalyst yielded N-9-beta- and N-9-alpha-; N-7-beta- and N-7-alpha-isomers, compounds 49-52, which were separated by silica gel column chromatography with two appropriate eluting solvent systems. Removal of the protecting groups gave compound 57 (beta-L-ddC) and the other 3 related isomers (58-60). The 2',3'-dideoxy-L-nucleoside analogues were tested in vitro against HIV-1, HBV, L1210, P388, S-180, and CCRF-CEM. 6-Amino-9-(2,3-dideoxy-beta-L-ribofuranosyl)purine (19, beta-L-ddA) was found to have antiviral activity against HBV with an ED(50) value of 6 mu M.

  DOI：

  10.1080/15257779508009755
• 作为产物：
  描述：

  乙酸酐 、 (R)-5-(tert-Butyl-diphenyl-silanyloxymethyl)-tetrahydro-thiophen-2-ol 在 吡啶 、 4-二甲氨基吡啶 作用下， 反应 2.0h， 生成 1-O-acetyl-5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-4-thio-L-ribofuranose
  参考文献：
  名称：

  2-（叔丁基二甲基甲硅烷氧基）噻吩：在2'，3'-二脱氧-4'-硫胞苷的两种对映体的总合成中的应用

  摘要：

  利用新型2-（叔丁基二甲基甲硅烷氧基）噻吩（1，TBSOT）作为通用的碳亲核试剂和甘油醛丙酮化物的两种对映体作为手性来源，这两种抗HIV活性2'，3'-dideoxy-4'-的对映体均进入设计并执行了硫胞苷10和ent-10 。

  DOI：

  10.1016/0040-4039(95)00162-6

文献信息

• The Utility of Furan-, Pyrrole-, and Thiophene-Based 2-Silyloxy Dienes As Demonstrated by Modular Synthesis of Annonaceous Acetogenin Core Units and Their Pyrrolidine and Thiolane Analogues
  作者：Franca Zanardi、Lucia Battistini、Gloria Rassu、Luciana Auzzas、Luigi Pinna、Lucia Marzocchi、Domenico Acquotti、Giovanni Casiraghi

  DOI：10.1021/jo991568x

  日期：2000.4.1

  diene modules, 2-[(tert-butyldimethylsilyl)oxy]furan (TBSOF), N-(tert-butoxycarbonyl)-2-[(tert-butyldimethylsilyl)oxy]pyrrole (TBSOP), and 2-[(tert-butyldimethylsilyl)oxy]thiophene (TBSOT) and suitable heteroatom-stabilized carbenium ions. By combining TBSOF, TBSOP, and TBSOT nucleophilic synthons with certain tetrahydrofuran, pyrrolidine, and thiolane acceptors, the construction of varied, adjacently

  我们报告了一种模块化的策略，用于获取无水产乙酸原素的核心单元及其氮和硫类似物，从而产生了巨大的结构多样性。该合成是基于重复性乙烯基加成方案的应用，该方案涉及独特的三联甲硅氧基二烯模块，2-[（叔丁基二甲基甲硅烷基）氧基]呋喃（TBSOF），N-（叔丁氧基羰基）-2-[（叔） -丁基二甲基甲硅烷基）氧基]吡咯（TBSOP）和2-[（叔丁基二甲基甲硅烷基）氧基]噻吩（TBSOT）和合适的杂原子稳定的碳正离子。通过将TBSOF，TBSOP和TBSOT亲核合成子与某些四氢呋喃，吡咯烷和硫杂环戊烷受体结合，可以确保构建与杂色产乙酸原素的核心片段相关的各种相邻相邻的寡杂环基序。首先，通过组装涵盖所有氧，氮和硫杂原子组合（即化合物7-9、13-15和19-21）的18个模型构造的集合，验证了枢轴耦合操纵的可靠性。然后，该统一的方案适用于伪造高级双-四氢呋喃，双-吡咯烷和双-硫杂环戊烷支架，这些支架涵盖了
• L-2',3'-dideoxy nucleoside analogs as anti-Hepatitis B (HBV) agents
  申请人：Yale University

  公开号：US05631239A1

  公开（公告）日：1997-05-20

  The present invention relates to the surprising discovery that certain dideoxynucleoside analogs which contain a dideoxy ribofuranosyl moiety having an L-configuration (as opposed to the naturally occurring D- configuration) exhibit unexpected activity against Hepatitis B virus (HBV). In particular, the compounds according to the present invention show potent inhibition of the replication of the virus in combination with very low toxicity to the host cells (i.e., animal or human tissue). Compounds according to the present invention exhibit primary utility as agents for inhibiting the growth or replication of HBV, HIV and other retroviruses, most preferably HBV.

  本发明涉及到一个惊人的发现，即某些二脱氧核苷类似物，其含有一个二脱氧核糖苷基团，该基团具有L构型（与天然的D构型相反），表现出出乎意料的对乙型肝炎病毒（HBV）的活性。特别地，本发明的化合物在与宿主细胞（即动物或人类组织）的毒性非常低的情况下，表现出对病毒复制的强效抑制。本发明的化合物主要用途是作为抑制HBV、HIV和其他逆转录病毒生长或复制的药剂，尤其是HBV。
• L-2',3'-dideoxy nucleoside analogs as anti-hepatitis B (HBV) and
  申请人：Yale University

  公开号：US05627160A1

  公开（公告）日：1997-05-06

  The present invention relates to the surprising discovery that certain dideoxynucleoside analogs which contain a dideoxy ribofuranosyl moiety having an L-configuration (as opposed to the naturally occurring D-configuration) exhibit unexpected activity against Hepatitis B virus (HBV). In particular, the compounds according to the present invention show potent inhibition of the replication of the virus in combination with very low toxicity to the host cells (i.e., animal or human tissue). Compounds according to the present invention exhibit primary utility as agents for inhibiting the growth or replication of HBV, HIV and other retroviruses, most preferably HBV. The compound 1-(2,3-dideoxy-beta-L-ribofuranosyl)-5-fluorocytosine is shown to be a potent anti-HIV agent with low toxicity to host cells.

  本发明涉及一个惊人的发现，即某些二脱氧核苷类似物，其中包含具有L-构型（与自然存在的D-构型相反）的二脱氧核糖苷基团，表现出意外的对乙型肝炎病毒（HBV）的活性。特别是，本发明的化合物在与宿主细胞（即动物或人类组织）具有非常低的毒性的情况下，显示出对病毒复制的强效抑制。本发明的化合物主要用途是作为抑制HBV、HIV和其他逆转录病毒生长或复制的药剂，最好是抑制HBV。化合物1-（2,3-二脱氧-beta-L-核糖呋喃苷）-5-氟胞嘧啶被证明是一种对宿主细胞毒性低的强效抗HIV药物。
• Method for treating HBV infections with
  申请人：Yale University

  公开号：US05561120A1

  公开（公告）日：1996-10-01

  The present invention relates to the surprising discovery that certain dideoxynucleoside analogs which contain a dideoxy ribofuranosyl moiety having an L-configuration (as opposed to the naturally occurring D- configuration) exhibit unexpected activity against Hepatitis B virus (HBV). In particular, the compounds according to the present invention show potent inhibition of the replication of the virus in combination with very low toxicity to the host cells (i.e., animal or human tissue). Compounds according to the present invention exhibit primary utility as agents for inhibiting the growth or replication of HBV, HIV and other retroviruses, most preferably HBV.

  本发明涉及一种惊人的发现，即某些含有L-构型（与天然存在的D-构型相反）的二脱氧核苷类似物，其含有二脱氧核糖苷基团，对乙型肝炎病毒（HBV）具有意想不到的活性。特别是，本发明的化合物在与宿主细胞（即动物或人类组织）的毒性非常低的情况下，表现出对病毒复制的强效抑制作用。本发明的化合物主要用作抑制HBV、HIV和其他逆转录病毒的生长或复制的药剂，其中最好是用于HBV的治疗。
• Modular Approach toward the Construction of the Core Motifs of Annonaceous Acetogenins and Variants Thereof
  作者：Franca Zanardi、Lucia Battistini、Gloria Rassu、Luigi Pinna、Marco Mor、Nicola Culeddu、Giovanni Casiraghi

  DOI：10.1021/jo972031r

  日期：1998.3.1